65 articles - From Saturday Apr 23 2022 to Friday Apr 29 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Am J Kidney Dis |
| Kidney Int |
Genetics in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Given the important contribution of genetic variants to CKD, practitioners with CKD patients are advised to "think genetic," which specifically involves obtaining a family history, collecting detailed information on age of CKD onset, performing clinical examination for extrarenal symptoms, and considering genetic testing. To improve use of genetics in nephrology, meeting participants advise developing an advanced training or subspecialty track for nephrologists, crafting guidelines for testing and treatment, and educating patients, students, and practitioners. Key areas of future research, including clinical interpretation of genome variation, electronic phenotyping, global representation, kidney-specific molecular data, polygenic scores, translational epidemiology, and open data resources, were also identified. |
meta-analyses and systematic reviews
| J Am Soc Nephrol |
Maturation of Glomerular Filtration Rate in Term-Born Neonates: An Individual Participant Data Meta-Analysis. These reference values for healthy term-born neonates show a biphasic increase in GFR with the largest increase between days 1 and 5. Together with the re-examined Schwartz equation, this can help identify altered GFR in term-born neonates. To enable widespread implementation of our proposed eGFR equation, validation in a large cohort of neonates is required. |
RCT, clinical trials, retrospective studies, etc…
| Am J Kidney Dis |
Apixaban Dosing Patterns Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation Receiving Dialysis: A Retrospective Cohort Study. Among patients with nonvalvular AF undergoing dialysis, warfarin is associated with an increased risk of bleeding compared to apixaban. The risk of bleeding with below-label apixaban was not detectably less than with label-concordant dosing. Label-concordant apixaban dosing is associated with a mortality benefit compared to warfarin. Label-concordant dosing, rather than reduced-label dosing, may offer the most favorable benefit/risk tradeoff for dialysis patients with nonvalvular AF. |
| Clin J Am Soc Nephrol |
Apixaban versus Warfarin for Treatment of Venous Thromboembolism in Patients Receiving Long-Term Dialysis. In a large group of US patients on dialysis with recent venous thromboembolism, we observed that apixaban was associated with lower risk of recurrent venous thromboembolism and of major bleeding than warfarin. There was no observed difference in mortality. |
Association of Phosphate-Containing versus Phosphate-Free Solutions on Ventilator Days in Patients Requiring Continuous Kidney Replacement Therapy. The use of phosphate-containing versus phosphate-free continuous KRT solutions was independently associated with fewer ventilator days and shorter stay in the intensive care unit. |
Dapagliflozin and Kidney Outcomes in Hospitalized Patients with COVID-19 Infection: An Analysis of the DARE-19 Randomized Controlled Trial. Dapagliflozin was well tolerated in participants with eGFR <60 and =60 ml/min per 1.73 m2. The effects of dapagliflozin on primary and secondary outcomes in hospitalized participants with COVID-19 were consistent in those with eGFR below/above 60 ml/min per 1.73 m2. Dapagliflozin was well tolerated and did not increase the risk of AKI in participants with eGFR below or above 60 ml/min per 1.73 m2. |
| Clin Kidney J |
Randomized comparison of three high-flux dialyzers during high-volume online hemodiafiltration-the comPERFORM study. FX CorAL 600 efficiently removed middle and small molecules and was superior to the two comparators in ß2-m RR. Albumin sieving kinetics point to reduced formation of a secondary membrane. |
| J Am Soc Nephrol |
Molecular Characterization of Membranous Nephropathy. These results suggest that relative to other glomerulonephropathies, MN has a distinctive molecular signature that includes upregulation of many podocyte-expressed genes, provide a molecular snapshot of MN, and facilitate insight into MN's underlying pathophysiology. |
| Kidney Int |
A novel unbiased method reveals progressive podocyte globotriaosylceramide accumulation and loss with age in females with Fabry Disease. There was no difference in F+ podocyte GL3 volume or volume fraction between age-matched males and females. Thus, in females with Fabry disease GL3 accumulation in F+ podocytes progresses with age in association with podocyte loss and proteinuria, and F+ podocyte GL3 accumulation in females with Fabry is similar to males, consistent with insignificant cross-correction between affected and non-affected podocytes. Hence, these findings have important pathophysiological and clinical implications. |
Blocking ribosomal protein S6 phosphorylation inhibits podocyte hypertrophy and focal segmental glomerulosclerosis. Since protein phosphatase 1 is known to negatively regulate rpS6 phosphorylation; treatment with an inhibitor increased phospho-rpS6 levels, promoted podocyte hypertrophy and exacerbated formation of FSGS lesions. Importantly, blocking rpS6 phosphorylation (either by generating congenic rpS6 knock-in mice expressing non-phosphorylatable rpS6 or by inhibiting ribosomal protein S6 kinase 1-mediated rpS6 phosphorylation with an inhibitor) significantly blunted podocyte hypertrophy, inhibited podocyte loss, and attenuated formation of FSGS lesions. Thus, our study provides genetic and pharmacologic evidence indicating that specifically targeting rpS6 phosphorylation can attenuate the development of FSGS lesions by inhibiting podocyte hypertrophy and associated podocyte depletion. |
Current kidney function parameters overestimate kidney tissue repair in reversible experimental kidney disease. The injury was particularly localized in the medulla, which is often not analyzed. Thus, recovery after crystal- or obstruction-induced CKD is characterized by ongoing tissue injury, fibrosis, and nephron loss, but not reflected by standard measures of kidney function. Hence, our data might aid in designing kidney recovery studies and suggest the need for biomarkers specifically monitoring intra-kidney tissue injury. |
Cyclin-dependent kinase 4-related tubular epithelial cell proliferation is regulated by Paired box gene 2 in kidney ischemia-reperfusion injury. Expression analyses of cell cycle-related genes showed that cyclin-dependent kinase 4 (CDK4) was significantly less expressed in the Pax2 knockout mice. In vitro data showed that the increase in CDK4 mRNA and protein expression induced by hypoxia was attenuated by EG1. Thus, Pax2 reactivation may be involved in PTEC proliferation by activating CDK4, thereby limiting kidney fibrosis. |
Endothelial-specific loss of Krüppel-Like Factor 4 triggers complement-mediated endothelial injury. To assess a potential mechanism by which KLF4 might regulate CD55 expression, we performed in silico chromatin immunoprecipitation enrichment analysis of the CD55 promotor and found KLF4 binding sites upstream from the CD55 transcription start site. Using patient-derived kidney biopsy specimens, we found glomerular expression of KLF4 and CD55 was reduced in patients with TMA as compared to control biopsies of the unaffected pole of patient kidneys removed due to kidney cancer. Thus, our data support that endothelial Klf4 is necessary for maintenance of a quiescent glomerular endothelial phenotype and its loss increases susceptibility to complement activation and induction of prothrombotic and pro-inflammatory pathways. |
Lay A TRAP for myeloid cell response in diabetic kidney disease. ATRAP is a type 1 angiotensin II receptor-associated protein that negatively regulates intracellular angiotensin II signaling. In this issue, Haruhara et al revealed that ATRAP deficiency of diabetic mice decreases anti-inflammatory macrophage infiltration and exacerbates albuminuria. The adoptive transfer and tubule-specific depletion of ATRAP highlight the crosstalk between glomerular injury and tubulointerstitial angiotensin II signaling and innate immunity. |
Metformin versus SGLT-2 inhibitors: how low can we go? In this issue, Corremans et al compare the effects of metformin and canagliflozin in rats with adenine-induced moderate (stage 2-4) chronic kidney disease. Metformin halted progression, whereas canagliflozin did not. This commentary puts the results in a wider clinical context. |
Mitochondrial pharmacotherapy during pregnancy and lactation in an ADPKD mouse model: a win for both mothers and their offspring. Pharmacotherapies that are safe during pregnancy are lacking for patients with autosomal dominant polycystic kidney disease. In this issue, Daneshgar et al reveal that administration of the mitochondrial-protective peptide, elamipretide, during pregnancy and lactation in a mouse model with autosomal dominant polycystic kidney disease, is nonteratogenic and attenuates disease severity in both mothers and their affected offspring. This finding suggests therapeutic potential of elamipretide during pregnancy, in utero, and in early postnatal life. |
Protein phosphatase 2Aca modulates fatty acid oxidation and glycolysis to determine tubular cell fate and kidney injury. Furthermore, PP2Aca also dephosphorylates p-Glut1 (Thr478) and suppresses Trim21-mediated Glut1 ubiquitination and degradation, leading to the promotion of glucose intake and glycolysis. Thus, this study adds new insight into the tubular cell metabolic alterations in kidney diseases. PP2Aca may be a promising therapeutic target for kidney injury. |
Regulation of T- and B-cell interactions determines the clinical phenotype associated with donor-specific antibodies. The cellular mechanisms that regulate donor-specific antibody formation and antibody-mediated rejection remain unknown. In this issue, Louis et al report that specific T-regulatory cell and B-regulatory transitional cell subsets are concomitantly diminished in patients with donor-specific antibody and consequent antibody-mediated rejection and advance alterations in specific cytokines and costimulatory molecules as important mechanisms by which these cells may suppress donor-specific antibody formation and, independently, progression to antibody-mediated rejection. |
Reticulon-1A mediates diabetic kidney disease progression through endoplasmic reticulum-mitochondrial contacts in tubular epithelial cells. Mechanistically, ER-bound RTN1A interacted with mitochondrial hexokinase-1 and the voltage-dependent anion channel-1 (VDAC1), interfering with their association. This disengagement of VDAC1 from hexokinase-1 resulted in activation of apoptotic and inflammasome pathways, leading to TEC injury and loss. Thus, our observations highlight the importance of ER-mitochondrial crosstalk in TEC injury and the salient role of RTN1A-mediated ER-mitochondrial contact regulation in DKD progression. |
The phenotype of HLA-binding B-cells from sensitized kidney transplant recipients correlates with clinically prognostic patterns of interferon- However, high frequencies of HLA-binding marginal-zone precursors associated with B-dependent interferon- |
Variation of the clinical spectrum and genotype-phenotype associations in Coenzyme Q10 deficiency associated glomerulopathy. A number of sequence variants, including putative local founder mutations, had divergent clinical presentations, in terms of onset age, kidney and non-kidney manifestations and kidney survival. Milder kidney phenotype was present in those with biallelic truncating variants within the COQ8B variant cohort. Thus, significant intra- and inter-familial phenotype variability was observed, suggesting both genetic and non-genetic modifiers of disease severity. |
Virus-related collapsing glomerulopathy, a common mechanism of injury? Collapsing glomerulopathy frequently shows focal lesions on biopsy, creating challenges with transcriptomic investigations because of inadequate tissue sample. This challenge is overcome with spatial transcriptomics, technology linking transcriptomic data to histology. Applying this technology to investigate patients with collapsing glomerulopathy related to HIV infection or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Smith et al provide provocative evidence that collapsing glomerulopathy may have different molecular signatures despite the similar morphologic appearance. |
| Nephrol Dial Transplant |
Effects of ferric citrate and intravenous iron sucrose on markers of mineral, bone, and iron homeostasis in a rat model of CKD-MBD. Oral FC improved phosphorus homeostasis, some iron-related parameters, and the production and cleavage of FGF23. The intermittent effect of low-dose IV iron sucrose on cardiovascular calcification and bone should be further explored in moderate-to advanced CKD. |
Hypophosphatemia in critically ill patients undergoing Sustained Low-Efficiency Dialysis with standard dialysis solutions. Hypophosphatemia is a frequent complication in critically ill patients undergoing SLED with standard dialysis solutions, that worsens with increasing SLED treatment intensity. In patients undergoing daily SLED, phosphate supplementation is strongly associated with reduced ICU mortality. |
Microvascular remodeling and altered angiogenic signaling in human kidneys distal to occlusive atherosclerotic renal artery stenosis. These observations underscore the nature of human RAS as a microvascular disease distal to main vessel stenosis, and support therapeutic strategies directly targeting the post-stenotic kidney microcirculation in patients with RAS. |
The European Green Deal and nephrology: a call for action by the European Kidney Health Alliance (EKHA). incorporation in concrete), registration systems of ecologic burden and platforms to exchange ecologic best practices. We also discuss how the European Green Deal offers real potential for supporting and galvanizing these urgent environmental changes. Finally, we formulate recommendations to professionals, manufacturers, providers, and policy makers on how this correction could be achieved. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Am J Kidney Dis |
| Clin J Am Soc Nephrol |
| Kidney Int |
| Nat Rev Nephrol |
Artificial intelligence-enabled decision support in nephrology. Realizing the clinical integration of AI applications will require cooperative, multidisciplinary commitment to ensure algorithm fairness, overcome barriers to clinical implementation, and build an AI-competent workforce. AI-enabled decision support should preserve the pre-eminence of wisdom and augment rather than replace human decision-making. By anchoring intuition with objective predictions and classifications, this approach should favour clinician intuition when it is honed by experience. |
Membranous nephropathy: new pathogenic mechanisms and their clinical implications. The subsequent identification of more proteins associated with MN, some of which are also endogenous podocyte antigens, might further advance the clinical characterization of MN, including its diagnosis, treatment and prognosis. Insights from studies in patients with MN, combined with the development of novel in vivo and in vitro experimental models, have potential to improve the management of patients with MN. Characterizing the interaction between autoimmunity and local glomerular lesions provides an opportunity to develop more specific, pathogenesis-based treatments. |
Letters to the editors and authors’ replies
| Kidney Int |
all remaining publications eg case reports, images of the month, etc…
| Clin J Am Soc Nephrol |
| J Am Soc Nephrol |
| Kidney Int |
| Nat Rev Nephrol |